Wide expressivity variation and high but no gender‐related penetrance in two dopa‐responsive dystonia families with a novel GCH‐I mutation
Identifieur interne : 003A87 ( Main/Exploration ); précédent : 003A86; suivant : 003A88Wide expressivity variation and high but no gender‐related penetrance in two dopa‐responsive dystonia families with a novel GCH‐I mutation
Auteurs : Antonino Uncini [Italie] ; Maria Vittoria De Angelis [Italie] ; Patrizia Di Fulvio [Italie] ; Michele Ragno [Italie] ; Grazia Annesi [Italie] ; Alessandro Filla [Italie] ; Liborio Stuppia [Italie] ; Domenico Gambi [Italie]Source :
- Movement Disorders [ 0885-3185 ] ; 2004-10.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- Adult, DNA Mutational Analysis, DNA, Single-Stranded (genetics), Dopamine Agonists (therapeutic use), Dystonia (drug therapy), Dystonia (genetics), Female, GTP Cyclohydrolase (genetics), Gene Expression (genetics), Gene penetrance, Genetic Variation (genetics), Haplotypes, Humans, Levodopa (therapeutic use), Male, Middle Aged, Mutation, Nervous system diseases, Pedigree, Phenotype, Point Mutation (genetics), Polymorphism, Genetic (genetics), Segawa disease, Sex, dopa‐responsive dystonia, expressivity, founder effect, gender‐related penetrance, parkinsonism.
- MESH :
- chemical , genetics : DNA, Single-Stranded, GTP Cyclohydrolase.
- chemical , therapeutic use : Dopamine Agonists, Levodopa.
- drug therapy : Dystonia.
- genetics : Dystonia, Gene Expression, Genetic Variation, Point Mutation, Polymorphism, Genetic.
- Adult, DNA Mutational Analysis, Female, Haplotypes, Humans, Male, Middle Aged, Pedigree, Phenotype.
Abstract
We describe the clinical and molecular correlates in two Italian families with dopa‐responsive dystonia (DRD) and the same novel mutation of GTP‐cyclohydrolase I (GCH‐I) gene. Thirty‐five subjects were examined and the genotype correlated to phenotype. Childhood onset foot dystonia is present in 7 subjects currently under the age of 40. In 1 patient bilateral foot dystonia was evident at birth suggesting that dystonia may be active as early as in utero. In another patient, dystonia spontaneously remitted in adolescence, to relapse 8 years later, as writer's cramp. Dystonia and parkinsonian signs are present in 5 other patients. In 2 subjects an isolated parkinsonism started over the age of 45. A 5‐base pair insertion at codon 242 within exon 6 of GTP‐cyclohydrolase I (GCH‐I) gene that shifts the reading frame and results in a premature stop at codon 247 with truncation of the polypeptide has been detected in 21 subjects. Considering dystonia and parkinsonism the overall penetrance is 0.71 and not significantly different in men (0.69) and women (0.75). Genealogical studies seem to exclude that these families are related but haplotype analysis suggests a single founder. Our findings in subjects with the same mutation indicate a wide intrafamilial variation in expressivity and high penetrance in DRD but do not confirm the reported influence of gender on GCH‐I gene mutation penetrance. © 2004 Movement Disorder Society
Url:
DOI: 10.1002/mds.20048
Affiliations:
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Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2004-10">2004-10</date><biblScope unit="vol">19</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="1139">1139</biblScope><biblScope unit="page" to="1145">1145</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">DED6D94EB72AD1976DD575957ED96B483ACCA049</idno><idno type="DOI">10.1002/mds.20048</idno><idno type="ArticleID">MDS20048</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>DNA Mutational Analysis</term><term>DNA, Single-Stranded (genetics)</term><term>Dopamine Agonists (therapeutic use)</term><term>Dystonia (drug therapy)</term><term>Dystonia (genetics)</term><term>Female</term><term>GTP Cyclohydrolase (genetics)</term><term>Gene Expression (genetics)</term><term>Gene penetrance</term><term>Genetic Variation (genetics)</term><term>Haplotypes</term><term>Humans</term><term>Levodopa (therapeutic use)</term><term>Male</term><term>Middle Aged</term><term>Mutation</term><term>Nervous system diseases</term><term>Pedigree</term><term>Phenotype</term><term>Point Mutation (genetics)</term><term>Polymorphism, Genetic (genetics)</term><term>Segawa disease</term><term>Sex</term><term>dopa‐responsive dystonia</term><term>expressivity</term><term>founder effect</term><term>gender‐related penetrance</term><term>parkinsonism</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA, Single-Stranded</term><term>GTP Cyclohydrolase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Dopamine Agonists</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dystonia</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Dystonia</term><term>Gene Expression</term><term>Genetic Variation</term><term>Point Mutation</term><term>Polymorphism, Genetic</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>DNA Mutational Analysis</term><term>Female</term><term>Haplotypes</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Pedigree</term><term>Phenotype</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Mutation</term><term>Pénétrance génique</term><term>Segawa maladie</term><term>Sexe</term><term>Système nerveux pathologie</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We describe the clinical and molecular correlates in two Italian families with dopa‐responsive dystonia (DRD) and the same novel mutation of GTP‐cyclohydrolase I (GCH‐I) gene. Thirty‐five subjects were examined and the genotype correlated to phenotype. Childhood onset foot dystonia is present in 7 subjects currently under the age of 40. In 1 patient bilateral foot dystonia was evident at birth suggesting that dystonia may be active as early as in utero. In another patient, dystonia spontaneously remitted in adolescence, to relapse 8 years later, as writer's cramp. Dystonia and parkinsonian signs are present in 5 other patients. In 2 subjects an isolated parkinsonism started over the age of 45. A 5‐base pair insertion at codon 242 within exon 6 of GTP‐cyclohydrolase I (GCH‐I) gene that shifts the reading frame and results in a premature stop at codon 247 with truncation of the polypeptide has been detected in 21 subjects. Considering dystonia and parkinsonism the overall penetrance is 0.71 and not significantly different in men (0.69) and women (0.75). Genealogical studies seem to exclude that these families are related but haplotype analysis suggests a single founder. Our findings in subjects with the same mutation indicate a wide intrafamilial variation in expressivity and high penetrance in DRD but do not confirm the reported influence of gender on GCH‐I gene mutation penetrance. © 2004 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>Italie</li></country></list><tree><country name="Italie"><noRegion><name sortKey="Uncini, Antonino" sort="Uncini, Antonino" uniqKey="Uncini A" first="Antonino" last="Uncini">Antonino Uncini</name></noRegion><name sortKey="Annesi, Grazia" sort="Annesi, Grazia" uniqKey="Annesi G" first="Grazia" last="Annesi">Grazia Annesi</name><name sortKey="De Angelis, Maria Vittoria" sort="De Angelis, Maria Vittoria" uniqKey="De Angelis M" first="Maria Vittoria" last="De Angelis">Maria Vittoria De Angelis</name><name sortKey="Di Fulvio, Patrizia" sort="Di Fulvio, Patrizia" uniqKey="Di Fulvio P" first="Patrizia" last="Di Fulvio">Patrizia Di Fulvio</name><name sortKey="Filla, Alessandro" sort="Filla, Alessandro" uniqKey="Filla A" first="Alessandro" last="Filla">Alessandro Filla</name><name sortKey="Gambi, Domenico" sort="Gambi, Domenico" uniqKey="Gambi D" first="Domenico" last="Gambi">Domenico Gambi</name><name sortKey="Ragno, Michele" sort="Ragno, Michele" uniqKey="Ragno M" first="Michele" last="Ragno">Michele Ragno</name><name sortKey="Stuppia, Liborio" sort="Stuppia, Liborio" uniqKey="Stuppia L" first="Liborio" last="Stuppia">Liborio Stuppia</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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